The long range goal of this work is to obtain a better understanding of the molecular mechanisms involved in cell mediated immunity. Emphasis will be placed on the further characterization of the natural cytotoxicity exhibited by normal human peripheral blood lymphocytes for cultured cell lines. We have demonstrated a multipliciy of antigens recognized by natural killer (NK) cells, with some target antigens shared by allogeneic cell lines. We will attempt to purify and characterize these target antigens. The receptor sites and the lytic mechanism(s) in natural cytotoxicity will also be further investigated and compared to antibody dependent and T cell mediated cytotoxic reactions. The premise that mitogen induced lysis is largely due to enhancement of natural cytotoxicity will also be further tested, and the enhancement of natural cytotoxicity by addition of insusceptible cell lines will be studied further. All of these experiments will be performed using a kinetic assay system that allows for accurate quantitation of cytotoxicity and for a meaningful comparison of different cytotoxicity systems.